Aging and aging associated diseases are likely to impart staggering health care costs upon the nation. Hence, there is a critical need to better understand biological aging through the characterization of the molecular changes associated with the aging process, so that potential targets for prevention and therapeutics can be more thoroughly explored. Since chronological age is the best predictor of biological age and age-related diseases, this initiative seeks to profile the metabolic differences between young and old populations of wild type C57BL/6 mice and subsequently study the impact of select stressors on the study population. In addition, since p38 signaling plays a major role in enhancing the expression of some senescence-related genes, stress responses will be investigated in p38a-mutant young and old mice. These mouse models will be used to establish a foundation for future research with human samples and subjects. This proposal is an extension of an ongoing project titled "Genomic and metabolomic responses to alcohol-induced liver damage" (5U01ES016013-02) and as such aims to broaden the scope of the original study. This project combines the unique expertise and experience of Frank J. Gonzalez's laboratory (National Cancer Institute) and Albert J. Fornace's laboratory. This competitive supplement will support studies on the effects of aging on injury responses by alcohol as well as select environmental toxicants. These studies will also contribute to the development of aging-associated biomarkers and the elucidation at the metabolomic level of changes occurring during stress-induced cellular senescence and biological aging.